The Nobel Prize in Physiology and Medicine for 2009

DOI: 10.1134/S0006297910050135

The Nobel Prize for 2009 has been awarded for discovery of telomeres and
telomerase. Telomeres are special DNA sequences on the ends of
chromosomes that prevent their degradation during replication and thus
ensure the genome stability. This problem has direct implications for
tumors, aging, and cloning of organisms.

The winners for the first time include two women, and both are Americans
(although Elisabeth Blackburn was born on the island of Tasmania). The
contribution of Blackburn to this discovery is doubtless. Even 15-20
years ago one might conclude that her experimental discoveries of
telomeres in an unicellular organism Tetrahymena and then of a
very unusual enzyme, telomerase, containing its own intrinsic RNA
primer for elongating telomeres would be awarded with the Nobel Prize,
especially because both these crucial works were performed in
Blackburn’s laboratory. Still as a very young researcher of this
laboratory, Carol Greider, detected in 1988 an enzymatic activity
elongating the telomeres. The Nobel Committee might
“include” her as a nominee for the Nobel Prize but also
might “not include” on consideration that she “simply
had been working” under Blackburn’s guidance. History of
the Nobel Prize awarding knows both types of examples of behavior
towards similar assistants to a discovery. Favorably for Greider, she
was “included”. This resulted in the youngest winner in
Physiology and Medicine, and, moreover, the second woman this year.
Hurrah!

In the lectures and contacts Elisabeth Blackburn, a University of
California San Francisco professor, reminds one of a kind well-balanced
mother. Her Australian breeding made her the very “model”
and she “keeps distance” excellently but is not at all
stiff. Carol Greider, a professor of Johns Hopkins University
(Baltimore), seems much more artless as a typical American.

The contribution of J. Szostak, American of British origin and Harvard
University professor, is also doubtless. In 1982 he conducted a crucial
experiment (also together with Blackburn) that confirmed the telomere
functioning in a heterologous system.

Thus, the abovementioned situation suggests that it would be more
correct to give Blackburn half of the Prize and to divide the other
half between Greider and Szostak.

Note that the most important components of the telomerase-associated
part of the work, which included purification, cloning, and
establishment of the telomerase structure and action mechanism remained
without reward. This work was performed by other researchers, and this
extremely difficult work is not yet considered as a discovery.

However, similarly to the previous year, the Prize awarding excited not
only the joy for Science and its creators but also a not very pleasant
feeling. It is well known that the biological problem of the
chromosomal end shortening during replication was first formulated in
1971 and 1973 in theoretical articles by the Russian biologist Aleksei
Matveevich Olovnikov who is now living among us. In fact, he predicted
the phenomena, which were discovered by Blackburn and her colleagues 15
years later, although at that time he did not and could not know
anything about the telomere structure or about the end-elongating
enzyme telomerase. In all fairness it must be said that Aleksei
Matveevich is not the only one who has not been given deserved
attention. Thus, the works establishing the action mechanism of
telomerase, which is a very interesting and unusual bicomponent enzyme
containing internal RNA primer for synthesis, have been mentioned
above. An extremely important discovery related to telomeres also
belongs to L. Hayflick, who established limits of cell replication
number in culture, which are directly related with the telomere
shortening to the least allowed length.

A possible trivial explanation for the unpleasant situation with A. M.
Olovnikov is that his theoretical works (initially published in the
“great and mighty Russian” and with the author’s own
vocabulary) were simply unknown to the Nobel Committee members (what is
“marginotomy” for them and what are they for
“marginotomy” – Olovnikov’s terminology).
Possibly, these works could be unknown in foreign countries. And
really, in the 1970s only a few Russian researchers were permitted to
visit conferences (and, unfortunately, A. M. Olovnikov was not one of
these). And he was a modest man not prone to self advertising.

But were these works really unknown? First, two prominent modern
scientists (their works directly concerned telomerase) who were reading
lectures in the educational immunology program in Moscow (www.oncoimmunology.ru) knew very well about
Olovnikov’s works and were glad to make acquaintance with him
personally. These are the Nobel Prize winner Prof. T. Czekh and the
first discoverer of oncogenes and tumor suppressors Prof. R. Weinberg
who himself is being nominated for the Nobel Prize for 20 years. In T.
Czekh’s laboratory telomerase was characterized, and the
carcinogenesis theory of Weinberg comprises both telomerase and
telomeres. Thus, the intellectuals knew the work of Olovnikov and
referred it as prophetic.

Second, the work by Olovnikov published in 1973 in Journal of
Theoretical Biology was cited more than 700 times and mainly by
foreign authors. And these are very serious citations, which eliminate
the hypothesis about “ignorance”.

Third, A. M. Olovnikov has published in the 1990s in significant
English-language journals some reviews connecting his theory with
telomeres (using the universally adopted terminology).

Thus, either it was a lack of PR campaign without which modern science
rarely exists (by the way, the campaign is not certainly driven by a
contestant), or the Nobel Committee in Physiology and Medicine does not
care for theoreticians. By the way, it should be noted that Olovnikov
had been working in experimental biology but not in the field of
telomeres. I suppose that if in the 1980-1990s he had obtained any
experimental result in favor of his own theory, the situation could be
quite different.

What conclusion can be extracted from this story for the future? It is
necessary to promote outstanding Russian works and to start from their
wide acknowledgement in their native country. The striking hypothesis
of Olovnikov was known for a long time to broad circles of Russian
biologists, and confirmation and enrichment of the hypothesis by the
discovery of telomeres and telomerase is also known at least for 15
years. And why he, a worker of the Russian Academy of Sciences, has not
been awarded any of various academy prizes up to now?1 Why
was he not nominated for any state or governmental prize or award? And
finally, why was not he given the doctoral degree without the defense
of the thesis? And why such remarkable scientists as Olovnikov have
virtually no chance for being selected into the Russian Academy of
Sciences. So, we shall not blame the Nobel Committee for everything.

But we can be glad that Aleksei Matveevich has many biological theories,
and some of them have been proposed after the hypothesis about
telomeres. Telomeres are ends of chromosomes but not of life. Let us
wish him good luck.

1 The situation has been partially corrected by a decision of
Demidov’s Prize Committee: Aleksei Matveevich Olovnikov has been
awarded this prize for 2009 among four outstanding Russian scientists.